Bioavailability of Two Combination Products of Dutasteride (0.5mg) and Tamsulosin Hydrochloride (0.2mg) in Asian Males. (ARI115707)

This study has been completed.
Sponsor:
Information provided by:
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT01471678
First received: October 13, 2011
Last updated: December 8, 2011
Last verified: December 2011
  Purpose

This study aims to determine the relative bioavailability of tamsulosin hydrochloride in a fixed dose combination capsule of dutasteride and tamsulosin hydrochloride (0.5 mg/0.2 mg) relative to co-administration of dutasteride 0.5 mg capsules and tamsulosin hydrochloride 0.2 mg tablets or capsules. Two fixed dose combination capsules will be tested; one will contain tamsulosin hydrochloride pellets with a 15% enteric coating, and the other tamsulosin hydrochloride pellets with a 10% enteric coat. In addition, two formulations of tamsulosin hydrochloride will be tested in the co-administration with dutasteride 0.5 mg; a 0.2 mg oral disintegrating tablet and a 0.2 mg hard shell capsule. This will be an open-label, randomized, single dose, four-period crossover in healthy male subjects of North East Asian ancestry. Subjects will receive single oral doses in four treatment periods, each separated by a 5-10 day washout period. Blood samples for pharmacokinetic analysis will be taken at regular intervals after dosing. Safety will be assessed by measurement of blood pressure, heart rate and review of adverse events. The study will enrol approximately 30 healthy male subjects to ensure that 24 complete the study.


Condition Intervention Phase
Prostatic Hyperplasia
Drug: Dutasteride (0.5mg)
Drug: FDC product of dutasteride (0.5mg) and tamsulosin HCl (0.2mg)
Drug: Harnal D Tablets and Harnal Capsules (both comprising 0.2 mg tamsulosin HCl)
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Bio-availability Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open-label, Randomized, Single Dose, Four-Period Crossover Study to Compare the Bioavailability of Fixed Dose Combination Capsule Formulations of Dutasteride and Tamsulosin Hydrochloride (0.5 mg/0.2 mg) With 10% and 15% of Enteric Coated Pellets With Harnal-D Tablets and Harnal Capsules Co-administered With Dutasteride (0.5 mg) Soft Gel Capsules in Healthy Male Subjects of North East Asian Ancestry

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Bioavailability of tamsulosin in 2 FDC formulations (Tamsulosin 0.2 mg and Dutasteride 0.5 mg) relative to co-administration of AVODART capsules with Harnal-D tablets or Harnal capsules in male subjects of Asian ancestry in the fed state [ Time Frame: From dosing to 72 hours post-dose ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Bioavailability of tamsulosin in one FDC formulation relative to the other FDC formulation (each capsule containing 0.2 mg tamsulosin HCl and 0.5 mg dutasteride) in healthy male subjects of Asian ancestry in the fed state. [ Time Frame: From dosing to 72 hours post-dose ] [ Designated as safety issue: No ]
  • Safety and tolerability of dosing with one FDC formulation relative to the other FDC formulation (each capsule containing 0.2 mg tamsulosin HCl and 0.5 mg dutasteride) in healthy male subjects of Asian ancestry in the fed state [ Time Frame: Vital signs from dosing to 72 hr post-dose. Adverse events monitoring from dosing to 72hr post-dose ] [ Designated as safety issue: No ]

Enrollment: 27
Study Start Date: June 2011
Study Completion Date: September 2011
Primary Completion Date: September 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Fixed dose combination product
Fixed Dose Combination capsule containing dutasteride 0.5mg and tamsulosin 0.2 mg
Drug: Dutasteride (0.5mg)
This study is an open-label, randomized, single dose, four-period cross-over study.
Drug: Harnal D Tablets and Harnal Capsules (both comprising 0.2 mg tamsulosin HCl)
a commercial formulation of dutasteride plus tamsulosin HCl (Harnal-D Tablet); (4): a commercial formulation of dutasteride plus tamsulosin HCl(Harnal Capsule). Each dosing session will be separated by a wash-out period of 5 to 10 days
Experimental: Dutasteride (0.5mg)
Commercial formulation of dutasteride
Drug: FDC product of dutasteride (0.5mg) and tamsulosin HCl (0.2mg)
FDC (with 10% enteric coated tamsulosin pellets); (2): FDC (with 15% enteric coated tamsulosin pellets);
Experimental: Harnal-D Tablets and Harnal capsules
Commercial formulations of Harnal-D Tablets and Harnal Capsules both comprising 0.2mg tamsulosin HCl
Drug: FDC product of dutasteride (0.5mg) and tamsulosin HCl (0.2mg)
FDC (with 10% enteric coated tamsulosin pellets); (2): FDC (with 15% enteric coated tamsulosin pellets);

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   20 Years to 45 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Healthy as determined by a responsible and experienced physician, based on a medical evaluation including medical history, physical examination, laboratory tests and cardiac monitoring. A subject with a clinical abnormality or laboratory parameters outside the reference range for the population being studied may be included only if the Investigator and the GSK Medical Monitor agree that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures.
  • Males between 20 and 45 years of age inclusive, at the time of signing the informed consent form.
  • Japanese ancestry defined as being born in Japan, having four ethnic Japanese grandparents, holding a Japanese passport or identity papers and being able to speak Japanese, or Korean ancestry defined as being born in Korea, having four ethnic Korean grandparents, holding a Korean passport or identity papers and being able to speak Korean, or Chinese ancestry defined as being born in China, Hong Kong, Singapore or Taiwan, having four ethnic Chinese grandparents, holding a Chinese passport or identity papers and being able to speak Chinese.

Japanese, Korean and Chinese subjects should also have lived outside their respective countries for less than 10 years.

  • Male subjects with female partners of child-bearing potential must agree to use one of the protocol-approved contraception methods .This must be followed from the time of the first dose of study medication until 45 days after the last dose.
  • BMI within the range 18 -28 kg/m2 (inclusive).
  • Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.
  • Single QTcB < 450 msec
  • AST, ALT, alkaline phosphatase and bilirubin less than or equal to 1.5xULN (isolated bilirubin greater than 1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin is less than 35%).

Exclusion Criteria:

Medical Condition Exclusions:

  • Poor metabolizer for CYP2D6 substrates as determined by genotyping of selected CYP2D6 variants at screening.
  • History of postural hypotension, dizziness, poor hydration, vertigo, vaso-vagal reactions or any other signs and symptoms of orthostasis, which in the opinion of the investigator could be exacerbated by tamsulosin and result in putting the subject at risk of injury.
  • Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones.
  • A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening
  • A positive test for HIV antibody.
  • Subject is mentally or legally incapacitated.

Medical Exclusions:

  • Use of prescription or non-prescription drugs, including vitamins, herbal and dietary supplements (including St John's Wort, Black Khosh, Dong Quai, Milk Thistle, licorice) within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is longer) prior to the first dose of study medication, unless in the opinion of the Investigator and GSK Medical Monitor the medication will not interfere with the study procedures or compromise subject safety.
  • History of sensitivity to tamsulosin hydrochloride or durasteride, components thereof or drugs of this class or a history of drug or other allergy that, in the opinion of the investigator or GSK Medical Monitor, contraindicates their participation.
  • A history of sensitivity to heparin or heparin-induced thrombocytopenia
  • The subject has participated in a clinical trial and has received an investigational product within the following time period prior to the first dosing day in the current study: 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer).
  • Exposure to more than four new chemical entities within 12 months prior to the first dosing day.

Lifestyle Exclusions:

  • A positive pre-study drug/alcohol screen. A minimum list of drugs that will be screened for include amphetamines, barbiturates, cocaine, opiates, cannabinoids and benzodiazepines.
  • History of regular alcohol consumption within 6 months of the screening visit defined by the following Australian guidelines:

Males: An average weekly intake greater than 21 units or an average daily intake greater than 3 units. One unit is equivalent to 270 mL of full strength beer, 470 mL of light beer, 30 mL of spirits and 100 mL of wine.

Subjects must be able and willing to abstain from beverages and foods containing alcohol 24 hours prior to and during the dosing day.

  • Consumption of red wine, grapefruit juice, grapefruit and related hybrids from 7 days prior to the first dose of study medication.
  • Where participation in the study would result in donation of blood or blood products in excess of 500 mL within a 56 day period.
  • Unwillingness or inability to follow the procedures outlined in the protocol.
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT01471678

Locations
Australia, New South Wales
GSK Investigational Site
Randwick, New South Wales, Australia, 2031
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

Publications:
Responsible Party: Cheri Hudson; Clinical Disclosure Advisor, GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT01471678     History of Changes
Other Study ID Numbers: 115707
Study First Received: October 13, 2011
Last Updated: December 8, 2011
Health Authority: Australia: Department of Health and Ageing Therapeutic Goods Administration

Keywords provided by GlaxoSmithKline:
Cross-over design
Pilot bioequivalence
North east Asian ancestry
GI198745
Tamsulosin hydrochloride
healthy male subjects
Bioequivalence
Dutasteride

Additional relevant MeSH terms:
Prostatic Hyperplasia
Hyperplasia
Prostatic Diseases
Genital Diseases, Male
Pathologic Processes
Tamsulosin
Dutasteride
Adrenergic alpha-1 Receptor Antagonists
Adrenergic alpha-Antagonists
Adrenergic Antagonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
5-alpha Reductase Inhibitors
Enzyme Inhibitors

ClinicalTrials.gov processed this record on July 26, 2014